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Biomedical subjects

A Varela

Publications and source records attributed to A Varela.

At least 19 recordsLinked to original sources

Influence of fasting on the effects of dimethylamiloride and oxfenicine on ischaemic-reperfused rat hearts.

To assess whether glycolysis, Na+-H+ exchange and oxidation of fatty acid derived from endogenous lipolysis are involved in the beneficial effects of 24-h fasting on the ischaemic - reperfused heart, it was studied the effects of inhibiting Na+ - H+ exchange using 10 muM dimethylamiloride and fatty acid oxidation using 2 mM oxfenicine, on the functional activity, lactate production and cell viability measured with tetrazolium stain. Since fasting accelerates heart fatty acid oxidation, data were compared to those from fed rats; using Langendorff perfused (glucose 10 mM) hearts of 250-350 g Wistar rats exposed to 25 min ischaemia - 30 min reperfusion. Fasting reduced the ischaemic rise of end diastolic pressure (contracture), improved recovery of contraction and lowered lactate production in comparison with the fed whereas cellular viability was similar in both groups. Dimethylamiloride improved the recovery of contraction (fed control 24 +/- 9%, fed treated 68 +/- 11%, P < 0.05 at the end of reperfusion), attenuated the contracture (fed control 40 +/- 9%, fed treated 24 +/- 11%, P < 0.05 at the beginning of reperfusion) and reduced lactate production in the fed group and increased cellular viability in both groups (fed control 21 +/- 6%, fed treated 69 +/- 7%, P < 0.05, and fasted control 18 +/- 7%, fasted treated 53 +/- 8%, P < 0.05). Oxfenicine reduced the recovery of contraction (fasted control 88 +/- 6%, fasted treated 60 +/- 11%, P < 0.05) and increased lactate production of fasted group and attenuated the contracture in the fed. These data suggest that beneficial effects of fasting owe, at least in part, to a lowered glycolysis probably secondary to the increased fatty acid oxidation and to the accumulation of energy supplying acyl esters. Dimethylamiloride slowing of glycolysis might explain functional improvement, whereas it seems unrelated to the protection on cell viability.

Amiloride↗

Effects of 5-hydroxydecanoate and ischemic preconditioning on the ischemic-reperfused heart of fed and fasted rats.

This investigation aimed to assess whether the mitochondrial ATP-sensitive potassium channel blocker 5-hydroxydecanoate (5-HD) could abolish the protection conferred by fasting and ischemic preconditioning (IPC) and to ascertain whether these effects are associated with glycogen breakdown and glycolytic activity. Langendorff perfused hearts of fed and 24-h fasted rats were exposed to 25 min ischemia plus 30 min reperfusion. IPC was achieved by a 3 min ischemia plus a 5 min reperfusion cycle. 5-HD (100 microM) perfusion begun 5 min before IPC or 13 min before sustained ischemia in the non preconditioned groups. Fasting improved the reperfusion recovery of contraction, decreased the contracture and the lactate production, increased glycogenolysis and did not affect the percentage of viable tissue. 5-HD abolished the effects of fasting on the contractile recovery but did not affect the contracture. 5-HD decreased the lactate production in the fed group, increased the preischemic glycogen content in both nutritional groups and did not affect the ischemic glycogen fall. IPC improved the contractile function but prevented the contracture only in the fed group, reduced lactate accumulation and glycogenolysis and evoked an increase of the viable tissue. 5-HD abolished the effects of IPC on the contractile recovery and did not affect its effect on the contracture, lactate production, glycogenolysis and viable tissue. These data suggest that the mitocondrial ATP-sensitive potassium channel is involved in the effects of fasting and IPC on the contractile function but the other cardioprotective and metabolic effects appear evoked through other mechanisms. Also suggest that besides the inhibition of the mitochondrial potassium channel, other mechanisms mediate the effects of 5-HD.

Animals↗

Urgent lung transplantation in Spain.

BACKGROUND: Lung donors are scarce and lung transplantation resources are limited. Because urgent lung transplantation (ULT) is assumed to yield poor results, its use is controversial. We assessed the outcome of patients who received ULT seeking to determine effectiveness and risk factors. PATIENTS AND METHOD: We collected data from every ULT performed in Spain during 5 years (1998-2002). The survival of patients was studied using Kaplan-Meier, Cox regression, and chi-square statistical analyses. We compared outcomes and perioperative mortality (over 30 days) for ULT procedures, analyzing the influence of certain variables (age, type of transplant, diagnosis, indication, and time on waiting list). RESULTS: Among 109 patients proposed for the procedure, 73 ULT were performed during the period. The most frequent indications were pulmonary fibrosis (19 cases) and cystic fibrosis (19 cases), showing the worst and the better survival rates, respectively. The bad prognosis, determined mainly by per operative mortality rate (35.62%), was significantly affected by age (worse for patients older than 40 years) and type of LT (single worse than double; P < .05). A longer time waiting for ULT also showed a worse prognosis (P < .005). CONCLUSIONS: Long-term survival after ULT shows that the procedure is effective and efficient for a select group of patients, despite the high per operative risk. ULT should be reserved for younger patients. It also requires performance in a short period (just a few days), initially rejecting a single lung transplant, provided that the patient is adequately monitored.

Humans↗

[Improvements in lung preservation: 3 years' experience with a low-potassium dextran solution].

OBJECTIVE: Lung preservation quality is a crucial factor in the success of a lung transplant. In October 2000 we stopped using Euro-Collins (EC) lung preservation solution and began using a low potassium dextran solution (Perfadex [PER]). The objective of the present study was to assess outcome with the 2 solutions. MATERIAL AND METHODS: We analyzed the results of 68 lung transplants in which PER was used and compared the results with those of a historical control group consisting of the same number of transplants in which EC was used. RESULTS: There were no significant differences in the ages and diagnoses of the recipients in the 2 groups. Waiting list time was longer in the PER group. The most frequent cause of donor death in the EC group was craniocerebral trauma (62%), whereas in the PER group it was cerebral hemorrhage (54%). In the PER group more double lung transplants were performed than in the EC group (78% and 53% respectively; P=.002). There were no differences in the use of extracorporal circulation or ischemia time between the 2 groups. Early graft function, based on the patient's oxygenation index (ratio of PaO2 to inspired oxygen fraction [FiO2]) on arrival at the intensive care unit, was similar in the 2 groups. The incidence of severe graft failure (PaO2/FiO2<150 mm Hg) was significantly lower in the PER group than in the EC group (16% and 37% respectively; P=.01). No significant differences in hours of mechanical ventilation or postoperative mortality between the 2 patient series were found. CONCLUSIONS: Use of the newer lung preservation solution --PER-- led to a 50% lower incidence of severe ischemia-reperfusion graft injury during the early recovery from lung transplantation.

Adolescent↗

Prolonged survival of an HIV-infected patient with multidrug-resistant Mycobacterium bovis infection treated with surgical resection.

We describe a case of multidrug-resistant tuberculosis due to Mycobacterium bovis in a human immunodeficiency virus-infected woman with good immunologic status. The patient presented with a hard mass measuring 10 cm in diameter on the lower left ribs and a lung nodule measuring 3 cm in diameter in the left superior lobe. No adequate pharmacological treatment was available. Both lesions were surgically resected. The patient has remained asymptomatic (without fever, cough, lymphadenopathy, or cutaneous masses) for 20 months, after discharge from the hospital.

Adult↗

Influence of fasting on the effects of diazoxide in the ischemic-reperfused rat heart.

This investigation aimed to assess whether the mitochondrial ATP-sensitive potassium channel opener diazoxide could reproduce the protection conferred by ischemic preconditioning and to ascertain whether its effects are associated with changes in glycogen breakdown and glycolytic activity. Hearts of fed and 24-h fasted rats were perfused with 10 mM glucose containing medium and exposed to 25 min no-flow ischemia plus 30 min reperfusion. Diazoxide (10 microM) perfusion was begun 10 min before ischemia and continued throughout the experiment. Fasting accelerated reperfusion recovery of contraction, reduced the post-ischemic contracture and decreased lactate accumulation during ischemia but had no effects on glycogen levels and cellular viability. Diazoxide, did not affect glycogen catabolism but improved reperfusion recovery of contraction. Furthermore, diazoxide reduced ischemic lactate accumulation and contracture amplitude only in the fed group whereas it improved cell viability in the fed and fasted groups. These data indicate that: 1) reduced lactate production which may attenuate myocyte acidification might explain, at least in part, the beneficial effects of diazoxide on mechanical function, although data obtained with the fasted rat hearts indicate that other mechanisms must be involved as well; 2) the reduction of lactate production occurring in the fed group, does not seem to be related to glycogenolysis; and 3) since diazoxide improved cell viability in the fasted rat group where it did not reduce glycolytic activity, other mechanisms may be responsible for this cytoprotective effect.

Animals↗

Successful bilateral lung transplantation from a methanol-poisoned donor.

The shortage of suitable organ donors is an important limiting factor that is making the evaluation of marginal donors necessary and, consequently, allowing expansion of standard donor criteria for organ removal. Lung procurement after methanol poisoning is anecdotal; in fact, there is only one published case in literature and that case showed a successful outcome. In this report, we describe a case of lung donation from a previously healthy individual who died from methanol poisoning. Both lungs were successfully implanted to a 20-year-old man who suffered from cystic fibrosis. This case report is new evidence that lung transplantation from methanol-poisoned donors may be safely performed with a good outcome.

Adult↗

Henneguya schizodon n. sp. (Myxozoa, Myxobolidae), a parasite of the Amazonian teleost fish Schizodon fasciatus (Characiformes, Anostomidae).

A new histozoic species of myxosporean (Henneguya schizodon n. sp.) is described from the Amazon River teleost fish Schizodon fasciatus Spix & Agassiz, 1892 (Characiformes, Anostomidae). The plasmodia, which showed asynchronous development, were located in the kidney of the host. The spore body was ellipsoidal and was 13.1 (12-14) micron long by 3.3 (3-4) micron wide. The total length of the spore was 28.9 (27-30) micron, and each value had a caudal process measuring 16.3 (15-17) micron. The polar capsules were 5.4 (5-6) micron long by 1.3 (1-1.5) micron wide, and each had a polar filament with 8-10 coils. The characteristics of the species were compared with nearly all the species described so far, including all the species reported from South American fishes. This comparison allows to consider the materials as a new species, and the name Henneguya schizodon n. sp. is proposed.

Animals↗

Non heart beating donors. Succesfully expanding the donor's pool.

OBJECTIVES: Expand the donors pool is one of the most hastening problems among transplant coordination teams all over the world. Our Hospital outlined thirteen years ago a specific policy to increase donors pool with non-heart-beating-donors program. METHODS: We have developed an specific program, called "code 9" to get donors from "previously healthy" people who die of sudden or unexpected death. Madrid has one of the best emergency medical services all over the world, with response time under eight minutes, and being able to perform all kind of advanced life support maneuvers in situ and during transfer to hospital. RESULTS: From 1989 we have reported the goodness of the program and the excellence of the organs transplanted. In Madrid, one of the most active communities in Spain in organ donors procurement, 33% of donors comes from this program. Organs and tissues obtained are of same or better quality than those obtained from encephalic death donors. CONCLUSIONS: Non-heart beating programs are a good option to increase donors pool.

Heart Arrest↗

Effect of acute nitric oxide synthase inhibition in the modulation of heart rate in rats.

Acute nitric oxide synthase inhibition with N G-nitro-L-arginine methyl ester (L-NAME) on chronotropic and pressor responses was studied in anesthetized intact rats and rats submitted to partial and complete autonomic blockade. Blood pressure and heart rate were monitored intra-arterially. Intravenous L-NAME injection (7.5 mg/kg) elicited the same hypertensive response in intact rats and in rats with partial (ganglionic and parasympathetic blockade) and complete autonomic blockade (38 +/- 3, 55 +/- 6, 54 +/- 5, 45 +/- 5 mmHg, respectively; N = 9, P = NS). L-NAME-induced bradycardia at the time when blood pressure reached the peak plateau was similar in intact rats and in rats with partial autonomic blockade (43 +/- 8, 38 +/- 5, 46 +/- 6 bpm, respectively; N = 9, P = NS). Rats with combined autonomic blockade showed a tachycardic response to L-NAME (10 3 bpm, P<0.05 vs intact animals, N = 9). Increasing doses of L-NAME (5.0, 7.5 and 10 mg/kg, N = 9) caused a similar increase in blood pressure (45 +/- 5, 38 +/- 3, 44 +/- 9 mmHg, respectively; P = NS) and heart rate (31 +/- 4, 34 +/- 3, 35 +/- 4 bpm, respectively; P = NS). Addition of L-NAME (500 micro M) to isolated atria from rats killed by cervical dislocation and rats previously subjected to complete autonomic blockade did not affect spontaneous beating or contractile strength (N = 9). In vivo results showed that L-NAME promoted a tachycardic response in rats with complete autonomic blockade, whereas the in vitro experiments showed no effect on intrinsic heart rate, suggesting that humoral mechanisms may be involved in the L-NAME-induced cardiac response.

Analysis of Variance↗

[Prognostic factors of early morbidity and mortality after lung transplantation].

OBJECTIVES: Despite years of experience with lung transplantation, the rate of perioperative mortality remains high. The objective of this study was to look at our experience in the early postoperative period following lung transplantation in an effort to identify possible pre-, intra- and postoperative risk factors associated with mortality. PATIENTS AND METHODS: A retrospective study of 68 consecutive patients receiving lung transplants over a period of 56 months. The conditions that led to transplantation were obstructive disease (40%), interstitial disease (33%) and suppurative disease (27%). Pre-, intra- and postoperative characteristics of donors and recipients were analyzed for their relation to morbidity and mortality. Statistical studies were done using SPSS 10.0 software. A p-value less than.05 was considered significant. Univariate analysis identified variables associated with the incidence of mortality in the postoperative recovery unit, and the variables with statistically significant associations were entered into multivariate analysis, using a logistic regression model to calculate odds ratio (OR) and 95% confidence intervals (CI). RESULTS: No donor variables correlated with mortality. Patients with suppurative lung disease had a lower mortality rate (0% vs 30%; P = 0.04). Mortality was related to ischemic time longer than 300 minutes (OR = 2) and the use of extracorporeal circulation (OR = 4). A PaO2/FiO2 ratio less than 150 during the first 24 hours following transplantation (OR = 5) and reoperation due to bleeding (OR = 12) were the variables showing the highest correlations with mortality during the early postoperative period. CONCLUSIONS: The mortality rate during the early postoperative period in our series was 22%. The survival rate was better in patients with suppurative lung disease. Bleeding that required reoperation and early graft dysfunction (defined in part by a PaO2/FiO2 ratio less than 150 during the first 24 hours) were the variables that best predicted death in the early postoperative period following lung transplantation.

Adolescent↗

Effects of fasting and hypoxic preconditioning on the hypoxic-reoxygenated ventricular strips of the rat heart.

The investigation aimed to assess the effects of hypoxic preconditioning in right ventricle strips of fed and 24-h fasted rats, which display a fast fatty acid catabolism, and to ascertain whether these effects are associated with changes in the tissue levels of long-chain acylCoA and acyl carnitine and glycolytic activity. Strips were mounted isometrically in Krebs-bicarbonate solution with 10 mM dextrose and paced at 1 Hz. Strips were exposed to 30 min hypoxia and 60 min reoxygenation with or without a previous preconditioning cycle of 5 min hypoxia followed by a 10 min reoxygenation. During hypoxia the fasted rat strips underwent a greater contracture with respect to the fed group. Preconditioning reduced the contracture strength and accelerated the post-hypoxic recovery only in the fasted rat strips. Hypoxia evoked an increase in the acylCoA and acyl carnitine tissue-contents of the strips which reached higher levels in the fasted than in the fed rat groups. Preconditioning had no effects on the content of these metabolites. During hypoxia lactate output was lower in the fasted than in the fed rat strips and preconditioning abolished this decrease. These data suggest that the protective effects of hypoxic preconditioning occur in the heart tissue predisposed to the oxidation of fatty acid and can not be ascribed to changes in the accumulation of acylCoA and acyl carnitine but could be due, at least in part, to an activation of glycolysis.

Acyl Coenzyme A↗

Influence of fasting on the effects of ischemic preconditioning in the ischemic-reperfused rat heart.

The effects of fasting and ischemic preconditioning (IP) on heart function of Langendorff-perfused rat hearts exposed to 25 min global ischemia plus 30 min reperfusion (RP), were correlated with lactate release and tissue-levels of long-chain acyl carnitine (LCCa) and CoA (LCCoA). IP was achieved by a 3 min ischemia plus a 5 min reperfusion cycle. Creatine kinase leakage was measured to assess the extent of cardiac injury. Fasting reduced the ischemic-induced contracture, improved RP recovery of mechanical function, reduced lactate release and increased the end-ischemia LCCoA and LCCa levels. Both in the fed and the fasted rat hearts IP delayed the pacemaker depression, reduced the amplitude of ischemic contracture and improved the RP recovery of contraction. However, IP reduced creatine kinase and lactate release only in the fed rat hearts. IP had no effects on tissue LCCa and LCCoA in both groups. These data suggest that: 1) beneficial effects of fasting may be ascribed, at least in part, to a reduced lactate production which may attenuate ischemic myocyte acidification and to the accumulation of fatty acyl esters which would favour citric acid cycle replenishment during RP. 2) beneficial effects of IP could be in part explained by the reduction of lactate production in the fed group although data obtained with the fasted rat heart indicate that another mechanisms must also be involved in the effects of IP. 3) accumulation of LCCoA and LCCa is not involved in the noxious effects of ischemia as well as in the protection effected by IP.

Animals↗